Lymphoid System - WordPress.com · 9/10/2019 · Lymphoid System Kristine Krafts, M.D. Lymphoid System Lecture Objectives • Describe the function, components, and circulation of

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Lymphoid SystemKristine Krafts, M.D.

Lymphoid System Lecture Objectives

• Describe the function, components, and circulation of lymph.

• Describe the following features of lymphoid organs:• Function of each organ• Classification as primary or secondary• Histologic regions and structures that are

characteristic of each organ• Location of B and T lymphocytes within each organ• Composition of the stroma

Lymphoid System Lecture Outline

• Introduction

• Primary lymphoid organs• Bone marrow• Thymus

• Secondary lymphoid organs• Lymph nodes• Spleen• MALT


• Introduction

• The main purpose of the lymphoid system is to detect and inactivate foreign substances, such as:• Invading microorganisms • Cells of transplanted organs• Foreign materials (like pollen)• Cancer cells

• Lymph also brings nutrients from blood vessels to cells and picks up waste products.

Function of the Lymphoid System

• Formed when interstitial fluid seeps into lymphatic vessels. Also contains lymphocytes, proteins, and sometimes bacteria or metastatic tumor cells.

• Composition varies in different body regions. Usually lymph is clear, but lymph draining the gut (called “chyle”) is milky and contains a lot of triglycerides.

• Lymphatic vessels eventually merge together and empty into the blood circulation via the thoracic duct and right lymphatic duct.

Lymph (Lymphatic Fluid)

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Thoracic duct

Rightlymphatic

duct • The stroma of all lymphoid organs except the thymus is composed of reticulin fibers.

• The stroma of the thymus is composed of cell processes of epithelial reticular cells.

Stroma of Lymphoid Organs

Reticular fibers (type III collagen) forming a network. These fibers are argyrophilic (stainable with silver stains).

• Lymphocytes• B lymphocytes• T lymphocytes• Natural killer (NK) cells

• All lymphocytes have surface receptors that recognize infected cells.

Cells of the Lymphoid System

• You can’t reliably tell the type of lymphocyte by looking under a microscope.

• You have to use a technique called flow cytometry to look for markers (molecules) on the surface of the cells.

• B cells, T cells and NK cells have different markers on their cell surfaces.

All lymphocytes look the same!*

* Pretty much. Sometimes T cells and NK cells are bigger and havelittle granules in the cytoplasm.

• Antigen-presenting cells:• Macrophages• Dendritic cells

• Other blood cells:• Mast cells• Neutrophils• Monocytes• Eosinophils

More Cells of the Lymphoid System

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There are two main ways lymphocytes fight intruders (like bugs): humoral and cellular immunity.

Humoral immunityB cells turn into plasma cells, which make antibodies. Antibodies coat and eliminate bugs.

Cellular immunityT cells turn into cytotoxic T cells (which kill cells infected with bugs) and helper T cells (which help other cells do their jobs).

Ridiculously Oversimplified Immunology Lymphoid System Lecture Outline

• Introduction


Lymphocytes arise, differentiate and become immunocompetent in primary lymphoid organs. There are two primary lymphoid organs:

• Bone marrowAll lymphocytes arise in the bone marrow. B cells and NK cells mature in the bone marrow.

• ThymusT cells mature here.

Primary (Central) Lymphoid Organs What do B cells do in primary and secondary

lymphoid organs?

• B lymphocytes and natural killer cells are formed and mature in bone marrow.

• They then leave bone marrow, populate secondary lymphoid organs, and recirculate through blood, epithelia, and connective tissue..

What do T cells do in primary and secondary

lymphoid organs?

• Immature T-cell precursors originate in the bone marrow.

• They then leave bone marrow and travel through blood to the thymus.

• They finish maturing in the thymus and leave as CD4+ and CD8+ cells (this will make more sense next year!)


• Introduction

• Primary lymphoid organs• Bone marrow

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Normal bone marrow biopsy Normal bone marrow biopsy

Normal bone marrow biopsy Lymphocytes


• Introduction


• Located in mediastinum

• Thymus consists of lobes, capsule, and septa. Septa incompletely divide the lobes into numerous lobules.

• Lobules have 2 regions:• Cortex is peripheral and darker staining.• Medulla is central and lighter staining.

Thymus

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Thymus, low power

Lobe

Lobules

Septae

Thymus, medium power

Cortex

Medulla

T cells (thymocytes) • T cells in the cortex are in various stages of

differentiation. • T cells in the medulla are mature.

Thymic epithelial reticular cells • Present in both the cortex and medulla.• Abundant cytoplasm, large lightly-staining

nuclei and long cytoplasmic processes attached to processes of adjacent cells by desmosomes.

Cells of the Thymus

Thymus, high power: T cells in the cortex

Thymus, high power: T cells in the medulla Thymus, high power: epithelial reticular cell

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Hassel corpuscle (closely-packed, concentric reticular cells) Thymus, high power: post-capillary venule

• T cell precursors from the bone marrow enter the thymus in the subcapsular region.

• In the outer cortex, T cells undergo active proliferation.

• In the deeper cortex, T cells undergo “selection.” If they can’t bind well enough to cell receptors, or if they bind too well to “self” cells, they die.

• So: many T cells are produced, but most (97%) die.

T Cells in the Cortex

• The remaining T cells survive and migrate to the medulla.

• Cells in the medulla include mature T cells and epithelial reticular cells.

• Hassall’s corpuscles are made of degenerating epithelial reticular cells and keratin filaments. Found only in medulla. Function unknown.

T Cells in the Medulla

• Mature T cells leave the thymus and enter the blood.

• Arterioles and capillaries in cortex are surrounded by epithelial reticular cells with tight junctions, forming a blood-thymus barrier which excludes most circulating antigens.

• Thymus has no afferent lymphatics, and does not filter lymph like a lymph node does.

T Cells in the Blood

• The thymus is well-developed before birth.

• The thymus is heaviest at puberty. After puberty, it involutes but never completely disappears.

• In old age, the thymus is composed mainly of connective tissue and fat, but it is still capable of producing lymphocytes.

Development and Involution of the Thymus

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The thymus in elderly people consists mostly of fat and connective tissue


• Introduction



Secondary lymphoid organs trap antigens and initiate immune responses. Lymphoid cells can undergo further maturation here too. There are three secondary lymphoid organs:

• Lymph nodes

• Spleen• Mucosa-associated lymphoid tissue (MALT)

Secondary (Peripheral) Lymphoid Organs

• Secondary lymphoid organs consist of lymphoid follicles and diffuse lymphoid tissue in different architectural arrangements.

• Main function: trap antigens and present them to circulating lymphocytes.

• Specific functions:• Lymph nodes: filter lymph• Spleen: filters blood• MALT: filters antigens that attempt

to cross mucosal surfaces

Secondary (Peripheral) Lymphoid Organs


• Introduction


• Secondary lymphoid organs• Lymph nodes

Hilum

Lymph node

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• Outer cortex contains round structures called lymphoid follicles (composed of B cells)

• Paracortex (inner cortex) contains T cells and high endothelial venules

• Medulla composed of cords (containing B cells and macrophages) and sinuses (containing reticular fibers, lymph, circulating cells and antigens)

Lymph Node Architecture

Lymph node: low power

Cortex Medulla

Lymph node

Capsule

Germinal center

Paracortex

Medullary cord

Medullary sinusMedulla

Cortex • Primary (unstimulated) follicles are composed of small, dark, mature lymphocytes.

• Secondary (stimulated) follicles are composed of:

• Germinal center: a lighter-staining central area containing larger lymphocytes

• Mantle zone: around germinal center; contains small, dark lymphocytes

Lymph Node Follicles

Lymph node: primary follicles

Capsule

Subcapsularsinus

Primary lymphoid

follicle

Lymph node: secondary follicles

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Secondary follicle with germinal center and mantle zone B cells are in follicles; T cells are in interfollicular areas

Lymph node: medullaLymph node: medulla

Medullary cords contain B

cells, plasma cells and

macrophages

Medullary sinuses contain reticular fibers,

lymph, circulating cells

and antigens

Medullary cord with tons of plasma cells (arrows) Medullary sinus with macrophages (1), reticular cells (2) and trabeculae (3)

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• The capsule and trabeculae consist of dense irregular connective tissue.

• The fine stroma consists of reticular connective tissue (fibroblasts and reticular fibers).

Lymph Node Stroma

Lymph node capsule and trabeculum

Afferent lymphatic vessels • Penetrate the capsule of the lymph node on

the convex side. • Carry lymph (with antigen and cells) from sites

of infection back to the lymph nodes.

Efferent lymphatic vessels • Leave through the the hilum. • Carry lymph (with lymphocytes) from the

lymph node and return them it to the blood.

Afferent and Efferent Lymphatic Vessels

• The hilum is a depression in the concave surface of the lymph node.

• Arteries and nerves enter at the hilum.

• Veins and efferent lymphatics leave at the hilum.

The Hilum

Hilum

Lymph node

Hilum

How does lymph flow through the node?

Afferent lymphatic brings lymph

Subcapsular sinus

Intermediate sinus

Medullary sinus

Efferent lymphatics take it away

Dump lymph into larger lymphatics, then

into blood

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• High-endothelial venules (venules with tall endothelial cells) in paracortex allow lymphocytes in blood vessels to adhere to endothelial cells and migrate across the vessel wall to the lymphoid tissue.

• Lymphocytes move from blood circulation to lymphatic circulation via high-endothelial venules.

High Endothelial Venules

High-endothelial venule in lymph node

• Lymphocytes enter the lymph node in arterial vessels in the hilum, travel through arterioles and capillaries to high-endothelial venules in paracortex.

• Lymphocytes squeeze between endothelial cells of high-endothelial venules and enter lymphatic circulation in the cortex of the lymph node.

• Lymphocytes leave the node via efferent lymphatic vessels in the hilum.

Flow of lymphocytes from blood to lymph in lymph node

Hilum

How do lymphocytes get from blood to lymph?

Hilar arterioles brings blood (and

lymphocytes)

Arterioles

Capillaries

High-endothelial venules

Lymphocytes leave HeV, enter lymphatic circulation

Lymphocytes leave through efferent lymph

vessels in hilum


• Introduction


• Secondary lymphoid organs• Lymph nodes• Spleen

• Immunologic filtration of blood (trapping of antigens)

• Activation and proliferation of lymphocytes

• Removal of old red cells, platelets and debris (by macrophages)

Functions of the Spleen

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• The parenchyma of spleen is called splenic pulp and consists of white pulp and red pulp.

• No cortex or medulla are present.

• Stroma consists of capsule, trabeculae, and reticular connective tissue.

• Hilum contains nerves, arteries and veins.

Structure of the Spleen

Spleen: super low power view

White pulp

Red pulp

Spleen: capsule

Capsule

White pulp

Red pulp

Spleen: trabeculae

Trabeculae

White pulp consists of:

Periarteriolar lymphatic sheaths (PALS)• Circular collections of T cells around

arterioles

Splenic follicles (nodules) • Just like secondary follicles in lymph

nodes, except with one more layer: the marginal zone

• Composed of B cells• Usually have arteriole at periphery

White Pulp of the Spleen

Spleen: white and red pulp

White pulp

Red pulp

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Spleen: cute follicle

Germinal center

Mantle zone

Marginal zone

Arteriole

Spleen: higher power of follicle

Germinal center Mantle zone Marginal zone

Spleen: periarteriolar lymphatic sheath (PALS)

Periarteriolar lymphatic sheath

Arteriole

Splenic sinuses (sinusoids) • Leaky vessels lined by specialized endothelial

cells (“stave cells”) and surrounded by rings of reticular fibers like hoops on a barrel

• Healthy red cells easily squeeze through!• Old or damaged red cells get stuck

Splenic cords (cords of Billroth) • Located between sinuses • Contain red cells, granulocytes, lymphocytes,

macrophages, platelets, and plasma cells

Red Pulp of the Spleen

Open and closed circulation

Open circulation

Closed circulation

Splenic sinusoids, cords and macrophages

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Spleen: splenic sinusoids

SinusoidsEndothelial cells

Spleen: cords of Billroth

Cords

Blood flow in the spleen


• Introduction



• Lymphoid tissue in mucosa and submucosa of digestive, respiratory, reproductive and urinary systems.

• Examples: tonsils, Peyer’s patches (ileum), lymphoid tissue in oral mucosa.

Mucosa-Associated Lymphoid Tissue (MALT)

MALT in lung

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Peyer’s patch in ileum Tonsils

• Tonsils are aggregates of lymphoid follicles beneath the epithelium of the posterior oral cavity and nasopharynx.

• Three tonsils:• Pharyngeal• Palatine• Lingual

• Pharyngeal

• Palatine

• Lingual

Three Types of Tonsils

• Pharyngeal• One tonsil in midline of nasopharynx• Surface epithelium: pseudostratified

ciliated columnar (sometimes with areas of stratified squamous)

• Surface has gentle folds but no crypts• Thin partial capsule along deep portion


• Pharyngeal

• Palatine• Two tonsils in lateral oropharynx• Surface epithelium: stratified squamous• 10-20 deep invaginations (crypts)• Thick partial capsule along deep portion


Palatine tonsil: super low power view

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Palatine tonsil: stratified squamous epithelium Palatine tonsil: lymphoid follicles

Palatine tonsil: crypt Palatine tonsil: sequestered crypt

Debris and pus (neutrophils)

Palatine tonsil: lymphocytes traversing epithelium

Endothelial cells

• Pharyngeal

• Palatine

• Lingual• Numerous small tonsils at base of tongue• Surface epithelium: stratified squamous• Each tonsil has one short crypt• No capsule• Closely associated skeletal muscle and

mucous salivary glands


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• Introduction



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Lymphoid System - WordPress.com · 9/10/2019 · Lymphoid System Kristine Krafts, M.D. Lymphoid System Lecture Objectives • Describe the function, components, and circulation of